KR960034194A - N- (3-benzofuranyl) urea derivative - Google Patents

Abstract

N- (3-benzofuranyl) urea derivatives are prepared by reacting 3-amino-substituted benzofuran with a suitable substituted isocyanate or isothiocyanate. The N- (3-benzofuranyl) urea derivative can be used as an active ingredient of a medicament for treating acute or chronic inflammatory diseases in particular.

Description

N- (3-benzofuranyl) urea derivative

Since this is a trivial issue, I did not include the contents of the text.

Claims (10)

An N- (3-benzofuranyl) urea derivative of the general formula (I) and salts thereof. Wherein A and D are the same or different and are hydrogen, straight or branched chain acyl or alkoxycarbonyl, respectively, of up to 6 carbon atoms, or alkoxycarbonyl, phenoxy or benzoyl of up to 6 carbon atoms, C6 straight or branched chain of less than or alkyl or halogen, carboxyl, cyano, nitro, trifluoromethyl, trifluoromethoxy or formula _{^{-OR 5, -S (O) a}} R 6, - (O- CH ₂ -CO) _b -NR ⁷ group of ^{R 8, -CO-NR 9 R} 10, -SO 2 -NR 11 R 12 or -NH-SO ₂ R ^{13 [wherein, R 5, R 6, R} 8, R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are the same or different and are hydrogen, C ₃ -C ₆ cycloalkyl, benzyl, or phenyl having up to three heteroatoms selected from the group consisting of N, S and O The ring may be fused and is substituted by halogen, cyano, nitro, or straight or branched chain alkyl of up to 6 carbon atoms. A substituted 5- to 7-membered saturated or unsaturated heterocycle; Straight or branched chain alkyl, alkenyl or acyl each having up to 8 carbon atoms; Or a phenyl which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, halogen, carboxy or straight-chain or branched alkoxycarbonyl of up to 6 carbon atoms, or R ⁵ represents a hydroxyl protecting group or a carbon number 6 or less straight chain or branched alkoxycarbonyl, or is substituted by a straight or branched chain acyl or alkoxycarbonyl, phenoxy or benzoyl each having 6 or less carbon atoms, hydroxyl, O, halogen, cyano, nitro, or a 5 to 7 membered unsaturated heterocycle optionally substituted by straight chain or branched chain alkyl of up to 6 carbon atoms, having up to 3 carbon atoms represents a straight-chain or branched alkyl, or R ⁵ is of the formula SO ₂ R ¹⁴ group (wherein, R ¹⁴ represents phenyl, trifluoromethyl or straight-chain or branched alkyl having 4 or less carbon atoms, a represents 0, 1 or 2, b represents 0 or 1, R ⁷ represents And R ¹³ represents C ₆ -C ₁₀ aryl, trifluoromethyl, or straight chain or branched chain alkyl having 6 or less carbon atoms, and R ¹ represents a prime number, a carbon number 6 straight or branched chain alkyl, an amino protecting group, or the formula -CO-R ¹⁵ group of the following [where, R ¹⁵ is hydroxyl, C 6 or less in a straight or branched chain alkoxycarbonyl, C ₃ -C ₆ cycloalkyl, Pyridyl, pyrrolidinyl, or straight or branched chain alkyl of up to 8 carbon atoms optionally substituted by halogen, carboxyl or straight or branched alkoxycarbonyl of up to 6 carbon atoms, or hydroxyl, carboxyl, Straight Or represents phenyl which is optionally substituted by a branched alkoxy or alkoxycarbonyl] a represents, L represents an oxygen or sulfur atom, R ² is R ³ are the same or different and represents hydrogen, a carbon number of 6 or lower cycloalkyl, each A straight or branched alkyl, alkoxycarbonyl or alkenyl having up to 8 carbon atoms, or a straight or branched chain alkyl, alkoxy or alkoxycarbonyl or acyl, each of which is halogen, cyano, nitro, carboxyl or up to 6 carbon atoms, Or benzoyl or C ₆ -C ₁₀ aryl optionally mono- or trisubstituted by identical or different substituents selected from the group R ⁵ and R ₆ , or R ² and R ³ together with the nitrogen atom form a 5 to 7 membered R ⁴ is selected from the group consisting of hydroxyl, theophyl, C ₃ -C ₆ cycloalkyl, halogen, nitro, tetra Is selected from the group consisting of straight or branched chain alkyl, alkoxy, alkoxycarbonyl or acyl, each having up to 8 carbon atoms, optionally substituted with one or more substituents selected from the group consisting of halogen, Or a halogen, or a group of the formula -NR ¹⁶ R ¹⁷ , -SR ¹⁸ , SO ₂ R ¹⁹ or O-SO ₂ R ²⁰ , wherein the group is optionally substituted by one or more of the substituents , R ¹⁶ and R ¹⁷ are the same as defined for R ⁷ and R ⁸ and are the same or different, or R ¹⁶ represents a hydrogen atom, R ¹⁷ represents a straight-chain or branched-chain acyl group having 6 or less carbon atoms, and R ¹⁸ represents match arbitrarily by a hydrogen or a straight or branched chain alkyl having 6 or less, R ¹⁹ and R ²⁰ represent the same or different and represents linear or branched alkyl, benzyl or phenyl having 6 or less carbon atoms; Or it represents an optionally substituted phenyl that is disubstituted by phenyl. Wherein A and D are the same or different and are hydrogen, straight or branched chain acyl or alkoxycarbonyl, each having 5 or less carbon atoms, or carboxyl, hydroxyl, alkoxycarbonyl having 5 or less carbon atoms, phenoxy or or optionally substituted 5 or less carbon atoms, straight or branched chain alkyl, benzoyl or by a fluorine, chlorine, bromine, methyl or general nitro, trifluoromethyl formula _{^{-OR 5, -S (O) a}} R 6, - (O-CH ₂ -CO) _b -NR ⁷ R ⁸ , -CO-NR ⁹ R ¹⁰ , -SO ₂ -NR ¹¹ R ¹² or -NH-SO ₂ R ¹³ wherein R ⁵ , R ⁶ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are the same or different and each is hydrogen, cyclopropyl, cyclopentyl, cyclohexyl or cyano, or fluorine, chlorine, bromine, iodine, cyano, nitro, Or branched < RTI ID = 0.0 > alkyl, < / RTI > Thiazolyl, thienyl, thiazolyl or thienyl; Straight or branched chain alkyl, alkenyl, or acyl having up to 6 carbon atoms; Or phenyl which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, bromine, iodine, carboxyl or straight-chain or branched alkoxycarbonyl of up to 5 carbon atoms, or R ⁵ is benzyl, acetyl, or tetrahydropyranyl, straight or branched chain acyl or alkoxycarbonyl having 4 or less carbon atoms, straight or branched chain alkyl having 6 or less carbon atoms substituted by phenoxyacyl or benzoyl, or fluorine, chlorine, bromine , Straight or branched chain alkyl of up to 6 carbon atoms substituted by cyano, nitro or pyridyl, imidazolyl, thienyl or furyl optionally substituted by straight chain or branched chain alkyl of up to 4 carbon atoms, or R < ⁵ > SO ₂ -R ¹⁴ (wherein, R ¹⁴ is a linear or branched alkyl of methyl or 3 carbon atoms or less and phenyl, trifluoromethyl or Represents the clearance), a denotes a number of 0, 1 or 2, b denotes a number of 0 or 1, R ⁷ denotes a linear or branched alkyl of a small number or carbon number of 3 or less, R ¹³ is phenyl, tri Fluoromethyl or straight chain or branched chain alkyl having 3 or less carbon atoms, R ¹ is a prime number, straight or branched chain alkyl having 4 or less carbon atoms, tert-butoxycarbonyl or a group of the formula -CO-R ¹⁵ Wherein R ¹⁵ is selected from the group consisting of hydroxyl, straight or branched chain alkoxycarbonyl having 4 or less carbon atoms, cyclopentyl, cyclohexyl, pyridyl, pyrrolidinyl or fluorine, chlorine, bromine, Linear or branched alkyl having 5 or less carbon atoms optionally substituted by branched alkoxycarbonyl, or hydroxyl, carboxyl or a phenoxy which is optionally substituted by straight chain or branched alkoxy or alkoxycarbonyl, Carbonyl a] a represents, L represents an oxygen or sulfur atom, R ² is R ³ are the same or different and represents hydrogen, cyclobutyl cyclopentyl, cyclohexyl, or each having 6 or less linear or branched alkyl, alkoxycarbonyl Or alkenyl, or by the same or different substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, carboxyl, cyano, nitro, or straight or branched chain alkyl, alkoxy or alkoxycarbonyl Or R ² and R ³ together with the nitrogen atom form a pyrrolidinyl, piperidinyl or morpholinyl ring, and R ⁴ is optionally substituted with hydroxyl, theophyl , Cyclopentyl, situheyl, fluorine, chlorine, bromine, iodine, nitro, tetrazolyl, thiazolyl, furanyl, pyridyl, trifluoromethyl, Which is mono- or trisubstituted by identical or different substituents selected from the group consisting of methyl, ethyl, trifluoromethyl, difluoromethyl, cyano, carboxyl, straight or branched chain alkyl, alkoxy, alkoxycarbonyl or acyl each having up to 6 carbon atoms N- (3-benzofuranyl) urea derivatives and salts thereof, which are optionally substituted by phenyl, optionally substituted by fluorine, chlorine or bromine. Wherein A and D are the same or different and are hydrogen, straight or branched chain acyl or alkoxycarbonyl, each having 4 or less carbon atoms, or carboxyl, alkoxycarbonyl having 4 or less carbon atoms, phenoxy or benzoyl optionally substituted carbon atoms of 3 or lower straight or branched chain alkyl, or fluorine, chlorine, bromine, nitro, cyano, trifluoromethyl trifluoromethoxy, or the formula _{^{-OR 5, -S (O) a}} R 6, - (O-CH ₂ -CO) _b -NR ⁷ R ⁸ , -CO-NR ⁹ R ¹⁰ , -SO ₂ -NR ¹¹ R ¹² or -NH-SO ₂ R ¹³ wherein R ⁵ , R ⁶ , Wherein R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are the same or different and are hydrogen, cyclopropyl, cyclopentyl, cyclohexyl or cyano, or a group consisting of fluorine, chlorine, bromine, iodine, cyano and nitro Lt; RTI ID = 0.0 > C3-C4 < / RTI > Pyridyl, amidazolyl, 1,3-thiazolyl or thienyl; Straight or branched chain alkyl, alkenyl, or acyl having up to 3 carbon atoms; Or phenyl which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, bromine, iodine, carboxyl or straight-chain or branched alkoxycarbonyl of up to 3 carbon atoms, or R ⁵ is benzyl, acetyl, or tetrahydropyranyl, or straight or branched chain alkoxycarbonyl having up to 3 carbon atoms, or carboxyl, hydroxyl, straight or branched chain acyl or phenoxy, benzoyl, alkoxycarbonyl , or pyridyl, Imada pyridazinyl or 4 carbon atoms or straight or branched chain alkyl of less than substituted by thienyl, or R ⁵ is -SO ₂ -R ¹⁴ (wherein, R ¹⁴ is a methyl or methyl and phenyl, trifluoromethyl A represents 0, 1 or 2, b represents 0 or 1, R ⁷ represents a prime number, methyl or ethyl, and R ¹³ Represents a phenyl group, a trifluoromethyl group or a methyl group; R ¹ represents a prime number, a straight chain or branched chain alkyl group having 3 or less carbon atoms, or a group of the general formula -CO-R ¹⁵ wherein R ¹⁵ is hydroxyl, Or a straight chain or branched alkoxycarbonyl group having 3 or less carbon atoms, such as fluorine, chlorine, bromine, carboxyl, or a straight or branched chain alkoxycarbonyl group having 3 or less carbon atoms, 4 or less straight chain or branched chain alkyl, or hydroxyl, carboxyl, or phenyl optionally substituted by straight chain or branched chain alkoxy or alkoxycarbonyl each having up to 3 carbon atoms, L represents an oxygen or sulfur atom , R ² is R ³ are the same or different and represents hydrogen, cyclobutyl cyclopentyl, cyclohexyl or a 5 or less carbon atoms, respectively straight-chain or branched alkyl, Al Cycloalkenyl or alkenyl or is substituted by the same or different substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, carboxyl, cyano, nitro, or straight or branched chain alkyl, alkoxy or alkoxycarbonyl randomly or benzoyl, or phenyl which is substituted to three days by, or R ² and R ^3, form a pyrrolidinyl ring together with the nitrogen atom to which R ⁴ is an optionally hydroxyl, thiophenyl, cyclopentyl, A straight or branched chain alkyl group having 5 or less carbon atoms, or a straight or branched chain alkyl group having 5 or less carbon atoms, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, fluorine, chlorine, bromine, iodine, nitro, tetrazolyl, thiazolyl, furanyl, pyridyl, trifluoromethyl, difluoromethyl, Alkoxy, alkoxy, alkoxycarbonyl or acyl. The term " alkyl " (3-benzofuranyl) urea derivatives and salts thereof, which are optionally substituted by phenyl which is optionally mono- or disubstituted by chlorine. The N- (3-benzofuranyl) urea derivative according to any one of claims 1 to 3 for use in therapy. Reacting a compound of the general formula (II) below with a compound of the general formula (III) in the presence of a base and / or auxiliaries, if necessary, in an inert solvent and if R ² / R ³ is hydrogen and L is O , Reacting a compound of formula (II) with a compound of formula (IIIa), and when R ² / R ³ is hydrogen and L is S, reacting the compound of formula (II) with NH ₄ SCN ( ^3- benzopurea) according to any one of claims 1 to 3, characterized in that, when R ¹ , R ² and / or R ³ is not hydrogen, the amino group is optionally derivatized by a conventional method. Yl) urea derivative. Wherein ^{R, A, D, R 1,} R 2, R 4 and L are the same as defined above and, E is a halogen. A composition comprising at least one N- (3-benzofuranyl) urea derivative according to any one of claims 1 to 3 and a pharmaceutically acceptable diluent. 7. The composition according to claim 6, for treating acute and chronic inflammation. A process for preparing a composition according to claims 6 and 7, characterized in that the N- (3-benzofuranyl) urea derivative is formulated in a suitable dosage form together with conventional adjuvants. Use of an N- (3-benzofuranyl) urea derivative according to any one of claims 1 to 3 for the preparation of a medicament. 10. The use according to claim 9 for the manufacture of a medicament for the treatment of acute and chronic inflammatory diseases. ※ Note: It is disclosed by the contents of the first application.